*Distributed
by Scientific Resources Program, NCID, CDC
**IND = Investigational New Drug (IND), Food and Drug Administration
***These products are not expected to be manufactured again by these
producers.

FORMULARY

I. Immunobiologic Agents Used Therapeutically

Botulism
Antitoxin Bivalent (Equine) Types A and B
Botulism Antitoxin bivalent (AB) is a refined and concentrated liquid
preparation of horse (equine) globulins modified by enzymatic digestion
(2). It is a licensed product supplied
in single dose vials.

In
the United States the antitoxin is available only from the CDC because
of its limited use and its relatively short expiration date. The
antitoxin is released only for suspected or actual cases of botulinum
toxin poisoning. The antitoxin is stored at CDC quarantine stations
located in major airports around the nation, ensuring delivery to
any location in the United States within hours. All suspected cases
of botulinum poisoning and the subsequent request for antitoxin
must be initiated through state or local health departments. The
decision to dispense the antitoxin is made by CDC medical epidemiology
staff after discussion with the treating physician. This allows
CDC and the state health departments to maintain effective botulism
surveillance and to detect outbreaks as soon as possible. Physicians
requesting botulinum antitoxin should contact the CDC at 770-488-7100.

Diphtheria
Antitoxin (Equine)
Diphtheria antitoxin is a sterile, aqueous solution of the refined
and concentrated proteins, chiefly globulins, containing antitoxic
antibodies obtained from the blood serum of horses that have been
immunized against diphtheria toxin (2).
It is used to prevent or treat diphtheria by neutralizing the toxins
produced by Corynebacterium diphtheriae (5).
Diphtheria antitoxin is available under an IND protocol through
the CDC and is released for actual or suspected cases of diphtheria.
The antitoxin is stored at CDC quarantine stations located in major
airports around the nation, ensuring delivery to any location in
the United States within hours. All suspected cases of diphtheria
and the subsequent request for antitoxin must be initiated through
state or local health departments. The decision to dispense the
antitoxin is made by CDC medical epidemiologists after discussion
with the treating physician. This allows the CDC and the state health
departments to maintain effective diphtheria surveillance and detect
outbreaks as soon as possible. Clinicians requesting diphtheria
antitoxin should contact the CDC diphtheria duty officer at 404-639-8257
during working hours (8:00am to 4:30pm) and the Director's Emergency
Operations Center (DEOC) at 770-488-7100 at any other time (6).

Vaccinia
Immune Globulin (VIG)
Vaccinia immune globulin is a sterile, non-pyrogenic solution of
globulin derived from the plasma of adult human donors who have
been vaccinated with vaccinia virus(smallpox vaccine)(2).
Vaccinia immune globulin is released from the CDC, under an IND
protocol, when indicated for the treatment of eczema vaccinatum,
vaccinia necrosum, ocular vaccinia, or severe generalized vaccinia
in persons who receive the smallpox vaccine. The CDC medical staff
can assist physicians in the diagnosis and management of patients
with suspected complications of vaccinia vaccination(7).

II.
Immunobiologic Agents Used Prophylactically

Botulinum Toxoid
Pentavalent (ABCDE) botulinum toxoid is a combination of aluminum
phosphate-adsorbed toxoid derived from formalin-inactivated type
A,B,C,D and E botulinum toxins, with formaldehyde and thimerosal
used as preservatives. Botulinum toxoid is not licensed; it is distributed
by the CDC under an IND protocol. The toxoid is used to protect
individuals from accidental exposure to botulinum toxins. It should
be administered only to individuals working in high risk laboratories
who are actively working or expect to be working with cultures of
Clostridium botulinum or the toxins (8).

Vaccinia
Vaccine
Vaccinia (smallpox) vaccine is a licensed preparation of infectious
vaccinia virus. The vaccinia is grown in the skin of a vaccinated
bovine calf (2). In 1982, the only
active licensed producer of vaccinia vaccine in the United States,
Wyeth Laboratories, discontinued production for general use, and,
in 1983, distribution to the civilian population was discontinued.
Smallpox vaccination has not been required for international travelers
since January 1982, and International Certificates of Vaccination
no longer include smallpox vaccination.

CDC
provides vaccinia vaccine for laboratory workers directly involved
with smallpox or closely related orthopox viruses (e.g., monkeypox
and vaccinia). Due to clinical trials involving recombinant vaccinia
virus vaccines, health-care workers (e.g., physicians and nurses)
may now be exposed to vaccinia and recombinant vaccinia viruses
and should be considered for vaccinia vaccination (7).

There
is no evidence that smallpox vaccination has any therapeutic value
in the treatment or prevention of recurrent herpes simplex infection,
warts, oral thrush, or any other diseases (7).
Requests for smallpox vaccine for these unapproved uses cannot be
granted.

Anthrax VaccineAnthrax Vaccine Adsorbed (AVA) is the only licensed human anthrax vaccine in the United States and is produced by Emergent Biosolutions in Lansing, Michigan. AVA is prepared from a cell-free filtrate of B. anthracis culture that contains no dead or live bacteria (9).

CDC provides anthrax vaccine for laboratory workers conducting research under federally funded projects who require routine vaccination based on their occupational risk.

Routine vaccination with AVA is indicated for persons engaged a) in work involving production quantities or concentrations of B. anthracis cultures and b) in activities with a high potential for aerosol production. Laboratorians using standard Biosafety Level 2 practices in the routine processing of clinical samples are not at increased risk for exposure to B. anthracis spores. The risk for persons who come in contact in the workplace with imported animal hides, furs, bone meal, wool, animal hair, or bristles has been reduced by changes in industry standards and import restrictions. Routine preexposure vaccination is recommended only for persons in this group for whom these standards and restrictions are insufficient to prevent exposure to anthrax spores. Routine vaccination of veterinarians in the United States is not recommended because of the low incidence of animal cases. However, vaccination might be indicated for veterinarians and other high-risk persons handling potentially infected animals in areas with a high incidence of anthrax cases (9).

III.
Drug Products Used Therapeutically

ArtesunateArtesunate, an investigational drug, is in the class of medications known as artemesinins, which are derivatives from the “quinghaosu” or sweet wormwood plant (Artemisia annua). It is a sesquiterpene lactone with an internal peroxide linkage. Artesunate may be used to treat documented cases of malaria that require a parenteral medication (10).

Bithionol
Bithionol (Lorothidol, Bitin), an investigational drug, is a phenolic
substance structurally related to hexachlorophene. Bithionol is
an alternative to the drug praziquantel for treating human paragonimiasis
(infection by Paragonimus species). It is also indicated for treatment
of fascioliasis (infection by Fasciola hepatica). Its use is limited
to treating either of these infections in patients who are unable
to use praziquantel because of previous idiosyncratic or allergic
reactions, or in whom a previous course of praziquantel failed to
eradicate the infection (11).

Dehydroemetine
Dehydroemetine (Mebadin), an investigational drug, is a close structural
analog of emetine and is indicated for the treatment of amebic dysentery
and/or extraintestinal amebiasis that fails to respond to metronidazole.
Since the early 1960s, dehydroemetine has been used in many areas
of the world where amebiasis is endemic (12).
With the development of metronidazole, the use of dehydroemetine
for amebic dysentery and liver abscess has decreased notably.

Diethylcarbamazine
(DEC)
Diethylcarbamazine citrate (Hetrazan), an investigational drug,
is an anthelmintic agent that does not resemble other antiparasitic
compounds. It is a synthetic organic compound which is highly specific
for several parasites and does not contain any toxic metallic elements.
DEC is indicated for treatment of individual patients with certain
filarial diseases. These diseases include: lymphatic filariasis
caused by infection with Wuchereria bancrofti, Brugia malayi, or
Brugia timori; tropical pulmonary eosinophilia; and loiasis. DEC
continues to be the mainstay for treatment of patients with lymphatic
filariasis and loiasis. (13, 14)

Melarsoprol
Melarsoprol (Mel B, Arsobal), an investigational drug, is an arsenical
compound with trypanosomicidal effects. It is indicated for the
treatment of African (Gambian and Rhodesian) sleeping sickness (trypanosomiasis)
with neurologic involvement and for the treatment of early African
(Gambian and Rhodesian) sleeping sickness that is resistant to treatment
with suramin or pentamidine. It has been used outside the United
States since 1949 for treating central nervous system African sleeping
sickness (15). Cases of African sleeping
sickness are rarely imported into the United States.

Nifurtimox
Nifurtimox (Bayer 2502, Lampit), an investigational drug, is a nitrofurfurylidene
derivative. It was developed for the treatment of Trypanosoma cruzi,
the causative agent of Chagas' disease. The drug is distributed
by CDC to treat patients with acute, subacute, or early chronic
Chagas' disease. Although few indigenous cases of Chagas' disease
have been described in the United States, cases may develop in laboratory
workers, immigrants, and U.S. citizens returning from Latin America
(e.g., Peace Corps volunteers, military personnel, and missionaries)
(16).

Pentostam
Pentostam (sodium stibogluconate; sodium antimony gluconate) is
a pentavalent antimony compound used for treatment of all forms
of leishmaniasis. The 3 major clinical syndromes in humans are visceral
(kala-azar), cutaneous (Oriental sore), and mucosal leishmaniasis.
Pentostam is a well-established antileishmanial agent that is used
in many countries of the world and is available to U.S. licensed
physicians under an IND protocol through the CDC (17, 18).

Suramin
Suramin (Bayer 205, Germanin, Moranyl, Fourneau 309, Belganyl, Naphuride,
Antrypol) was introduced in 1920 for the treatment of African trypanosomiasis
(sleeping sickness). Suramin is considered the drug of choice for
the therapy of early Trypanosoma brucei rhodesiense sleeping sickness
when the central nervous system is not involved. Currently, pentamidine
is thought to be more effective than suramin for the therapy of
early sleeping sickness due to Trypanosoma brucei gambiense.

Suramin has also been used to destroy the adult worm (Onchocerca
volvulus) in onchocerciasis but, due to its toxicity, it is rarely
used for this. Ivermectin is considered the primary agent for treatment
of onchocerciasis. Suramin has also demonstrated antitumor activity
against prostatic, ovarian, and adrenocortical carcinoma. However,
appropriate dose, efficacy, and safety have not been established
for treatment of neoplasms.*
The CDC supplies suramin under an IND protocol to licensed physicians
(19).

Use
of trade names is for identification only and does not imply endorsement
by the U.S. Department of Health and Human Services.